PCOS: Polycystic Ovarian Syndrome NURS 541: Women’s Healthcare – Diagnosis and Management

Objectives Etiology Clinical Presentation Assessment Diagnosing PCOS Management Patient Counseling

Introduction Classified as a hyperandrogenic disorder Affects 6-8% of women Approximately 70% of women with clinical features of PCOS have the disorder

Etiology Imbalance of several reproductive hormones Dehydroepiandrosterone sulfate (DHEA-S) Dehydroepiandrosterone (DHEA) Androstenedione Testosterone Most testosterone is bound to sex hormone-binding globulin (SHBG) The amount of free testosterone dictates the amount of hyperandrogenic effects that are seen

Etiology SHBG free testosterone effects SHBG levels (and therefore the amount of testosterone binding) are influenced by hormonal changes Estrogen and thyroid hormone INCREASE levels Androgens and insulin DECREASE levels SHBG free testosterone effects Testosterone converted into dihydrotestosterone (DHT) by 5α reductase (enzyme) DHT responsible for androgenic symptoms

Etiology Women with PCOS have more steady levels of gonadotropins and sex hormones than women without PCOS Gonadotropin-releasing hormone (GnRH), and therefore luteinizing hormone (LH) pulse frequently versus with the menstrual cycle Increased level of LH => decreased follicle-stimulating hormone (FSH) Decreased ovulation

Etiology Typical cyclical LH surge (below) compared to the frequent LH surges seen in PCOS (left)

Etiology Determining the cause of the increased androgen production is key to individualized treatment Is it an issue of excess insulin? Is it an issue of decreased thyroid hormone? Is there too little estrogen? Is there too much DHEA/DHEA-S/androstenedione?

Clinical Presentation

Clinical Presentation Signs Associated conditions Hirsutism Obesity Alopecia Infertility Acne Insulin resistance Menstrual irregularities Dyslipidemia Polycystic ovaries Metabolic syndrome Virilization Psychological effects Cancer risks

Signs/Symptoms Hirsutism Alopecia Acne Excessive hair growth in most androgenic-sensitive areas (face, chin, upper lip, areolae, lower abdomen, inner thighs, perineum) Alopecia Androgen-related hair loss, usually frontal/crown region Acne Enlargement of sebaceous glands, sebum

Signs/Symptoms Menstrual Irregularities Polycystic ovaries Irregular menses, anovulatory cycles Possible heavy menses due to persistent endometrial stimulation, endometrial hyperplasia If normal cycles, may be still anovulatory – lack of premenstrual symptoms indication Polycystic ovaries As a result of chronic anovulation One or more ovaries with 12+ enlarged follicles and/or enlarged ovarian volume over 10mL (2003 ESHRE/ASRM consensus)

Signs/Symptoms Virilization Cluster of symptoms including clitoral hypertrophy, severe hirsutism, deepening of the voice, increased muscle mass, breast atrophy, and male pattern baldness If rapidly progressing, may indicate less common cause of hyperandrogenism Ovarian or adrenal tumor Congenital adrenal hyperplasia Hyperthecosis

Associated conditions Obesity Approximately ½ of all women with PCOS are obese Insulin resistance Affects 50-70% of women with PCOS Instrumental in hormonal changes associated with hyperandrogenism Increases risk for Type 2 Diabetes and glucose intolerance Dyslipidemia 70% of women with PCOS have at least 1 elevated lipid level

Associated conditions Metabolic syndrome Cluster of conditions – obesity, insulin resistance, dyslipidemia Increases risk for CV disease and diabetes Diagnostic criteria - 3 or more of the following: Waist circumference ≥ 35 inches Triglycerides ≥ 150mg/dL HDL cholesterol ≤ 50 mg/dL Systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 85 mmHg Fasting glucose ≥ 100 mg/dL

Associated conditions Infertility Related to anovulation More than ½ of women with PCOS are fertile, although may take longer to conceive Psychological effects Higher rates of depression, anxiety, binge eating higher for women with PCOS Cancer risks 3-fold increased risk of endometrial cancer 2-fold increased risk of ovarian cancer

Differential Diagnosis

Differential Diagnosis PCOS (80%) Nonclassical congenital adrenal hyperplasia (2%) Hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) syndrome (4%) Androgen-producing tumors (rare) – ovarian or adrenal Idiopathic hirsutism (5%) Thyroid disorders, androgenic medication, pregnancy, hyperprolactinemia, Cushing syndrome

Assessment

Assessment History Thorough menstrual history (menarche, menstrual pattern, flow, symptoms) Pregnancy history (ability to conceive, time to conception) Symptoms/associated conditions of PCOS, including onset and severity – rapid vs slow onset Medication history Family history of associated conditions

Assessment Physical Exam Anthropometric measurements – height, weight, BMI, waist circumference Blood pressure Skin examination – look for hirsutism, acne, alopecia Acanthosis nigricans often seen with insulin resistance Thyroid exam Breast exam Pelvic exam – assess for uterine/ovarian masses

Assessment Laboratory testing Mixed evidence re: appropriate testing Testing should reflect findings in history/exam Hyperandrogenism and ovulatory dysfunction TSH, prolactin, fasting lipid profile, 2hr OGTT (ACOG, AEPCOS, 2009) Hyperandrogenism and regular menstrual cycles Above, PLUS serum progesterone on day 20-24 of cycle Less than 3-4 ng/mL = oligo-ovulatory cycle

Assessment Laboratory testing (continued) Imaging/Procedures Testosterone testing – mixed evidence as to usefulness If tumor suspected, total testosterone recommended, and refer if > 150 ng/dL (100 ng/dL if menopausal) 17-OHP (hydroxyprogesterone) If congenital adrenal hyperplasia is suspected Imaging/Procedures Pelvic ultrasonography To identify ovarian cysts and endometrial hyperplasia Endometrial biopsy – chronic anovulation

Diagnosing PCOS

Differential Diagnosis PCOS (80%) Nonclassical congenital adrenal hyperplasia (2%) Hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) syndrome (4%) Androgen-producing tumors (rare) – ovarian or adrenal Idiopathic hirsutism (5%) Thyroid disorders, androgenic medication, pregnancy, hyperprolactinemia, Cushing syndrome

Diagnosing PCOS Two established criteria: Rotterdam PCOS Consensus Group (2004) Two of three of the following: Oligo- or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries Androgen Excess and Polycystic Ovary Syndrome Society Hyperandrogenism: hirsutism and/or hyperandrogenemia Ovarian dysfunction: oligo-anovulation and/or polycystic ovaries Exclusion of other androgen excess or related disorders

Management

Management Non-pharmacologic modalities Lifestyle modification – diet, nutrition, exercise Mechanical hair removal

Management Pharmacologic modalities Combined hormonal contraceptives Progestin with a non- or low androgenic potential preferred Desogestrel, norgestimate, drospirenone Signs/symptoms may be reduced/resolve within 2-12 months Help protect against endometrial hyperplasia with monthly withdrawal bleeds

Management Pharmacologic modalities Progestogens Anti-androgens To prevent endometrial hyperplasia and cancer LNG-IUS, progestin-only pills, DMPA, implant Medroxyprogesterone acetate 5-10mg or 200mg micronized progesterone first 14 days of each month Anti-androgens For refractory hirsutism or alopecia May be teratogenic so need effective contraception

Management Pharmacologic management (continued) Insulin sensitizing agents Metformin – if impaired glucose tolerance, inability to lose weight with diet and exercise or with those at normal weight Not recommended for treatment of PCOS symptoms Also helpful for those with infertility Topical agent Eflornithine HCl 13.9% (Vaniqa) – to treat hirsutism

When to Refer If diagnosis other than PCOS If initial treatment not successful Women with infertility issues (not successful with metformin) If metabolic syndrome present

Patient Counseling Follow up is necessary due to long-term risks of PCOS Weight management, nutrition, exercise Screening and management of BP, lipids, diabetes Management of menstrual cycle, withdrawal bleeds Support, encouragement, woman-centered care

Questions?